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1.
Nat Mater ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026087

RESUMEN

Iron-based 1111-type superconductors display high critical temperatures and relatively high critical current densities Jc. The typical approach to increasing Jc is to introduce defects to control dissipative vortex motion. However, when optimized, this approach is theoretically predicted to be limited to achieving a maximum Jc of only ∼30% of the depairing current density Jd, which depends on the coherence length and the penetration depth. Here we dramatically boost Jc in SmFeAsO1-xHx films using a thermodynamic approach aimed at increasing Jd and incorporating vortex pinning centres. Specifically, we reduce the penetration depth, coherence length and critical field anisotropy by increasing the carrier density through high electron doping using H substitution. Remarkably, the quadrupled Jd reaches 415 MA cm-2, a value comparable to cuprates. Finally, by introducing defects using proton irradiation, we obtain high Jc values in fields up to 25 T. We apply this method to other iron-based superconductors and achieve a similar enhancement of current densities.

2.
Medicina (Kaunas) ; 59(11)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38004063

RESUMEN

The diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. Moreover, pulmonary involvement in adult T-cell lymphoma (ATL) is often difficult to diagnose, especially in cases without characteristic flower cells. Here, we present the case of a 78-year-old man, in whom pathological examination of the transbronchial lung biopsy (TBLB) specimen did not reveal malignant findings; therefore, transbronchial lung cryobiopsy (TBLC) in combination with endobronchial ultrasonography (EBUS) was used to diagnose ATL based on the pathological findings. A literature review identified 18 cases of pulmonary lymphomas diagnosed using TBLC. Among the 19 cases, including our own, 16 cases were of B-cell lymphoma (84.2%), and the present case is the first case of ATL diagnosed using TBLC. Eighty percent of the cases underwent a biopsy (more than two samples) of the middle or lower lobe and were diagnosed without major complications. EBUS was used with TBLC in three cases to identify the location of the pulmonary lesions. In the present case, EBUS was also useful for avoiding vascular biopsy. Although large-scale prospective studies are required to establish precise guidelines for diagnosing pulmonary lymphomas using TBLC, our case report and review contributes to a deeper understanding of the diagnosis of rare diseases.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Linfoma de Células T , Linfoma , Masculino , Humanos , Adulto , Anciano , Enfermedades Pulmonares Intersticiales/diagnóstico , Broncoscopía/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología , Biopsia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Linfoma/patología , Linfoma de Células T/patología
3.
Rinsho Ketsueki ; 64(2): 97-101, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-36990739

RESUMEN

A 55-year old female patient was treated with methotrexate (MTX) and infliximab (IFX) for rheumatoid arthritis (RA). She experienced unknown fever, generalized lymphadenopathy, and liver tumors. Histological examination of the inguinal lymph node and a liver tumor resulted in the pathological diagnosis of classic Hodgkin lymphoma, with many Reed-Sternberg cells with the positivity of Epstein-Barr virus (EBV). She was diagnosed with MTX-related lymphoproliferative disorders (MTX-LPDs). She received chemotherapy after the cessation of MTX and IFX and achieved complete remission. RA showed recurrence after a while, and she was treated with steroids or other drugs. Six years after the chemotherapy, she experienced low-grade fever and anorexia. Whole computed tomography images showed an appendix tumor and enlargement of the surrounding lymph nodes. Appendectomy with the radical lymph nodes dissection was performed. The pathological diagnosis was diffuse large B-cell lymphoma, resulting in the clinical diagnosis of the relapse of MTX-LPD. EBV was negative at this point. The pathological findings of MTX-LPD may change at relapse; thus, biopsy should be considered when the relapse of MTX-LPD is suggested.


Asunto(s)
Artritis Reumatoide , Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Femenino , Humanos , Persona de Mediana Edad , Metotrexato/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Herpesvirus Humano 4 , Recurrencia Local de Neoplasia/tratamiento farmacológico , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/diagnóstico
4.
Cancer Sci ; 113(12): 4092-4103, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36047964

RESUMEN

Adult T-cell leukemia/lymphoma (ATL) is an intractable hematological malignancy with extremely poor prognosis. Recent studies have revealed that super-enhancers (SE) play important roles in controlling tumor-specific gene expression and are potential therapeutic targets for neoplastic diseases including ATL. Cyclin-dependent protein kinase (CDK) 9 is a component of a complex comprising transcription factors (TFs) that bind the SE region. Alvocidib is a CDK9 inhibitor that exerts antitumor activity by inhibiting RNA polymerase (Pol) II phosphorylation and suppressing SE-mediated, tumor-specific gene expression. The present study demonstrated that alvocidib inhibited the proliferation of ATL cell lines and tumor cells from patients with ATL. RNA sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) disclosed that SE regulated IRF4 in the ATL cell lines. Previous studies showed that IRF4 suppression inhibited ATL cell proliferation. Hence, IRF4 is a putative alvocidib target in ATL therapy. The present study revealed that SE-mediated IRF4 downregulation is a possible mechanism by which alvocidib inhibits ATL proliferation. Alvocidib also suppressed ATL in a mouse xenograft model. Hence, the present work demonstrated that alvocidib has therapeutic efficacy against ATL and partially elucidated its mode of action. It also showed that alvocidib is promising for the clinical treatment of ATL and perhaps other malignancies and neoplasms as well.


Asunto(s)
Antineoplásicos , Leucemia-Linfoma de Células T del Adulto , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Genes Relacionados con las Neoplasias , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/patología , Antineoplásicos/farmacología , Elementos de Facilitación Genéticos , Regulación Leucémica de la Expresión Génica
5.
Br J Haematol ; 196(3): 629-638, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34632569

RESUMEN

'Monitoring of immune responses following mogamulizumab-containing treatment in patients with adult T-cell leukaemia-lymphoma (ATL)' (MIMOGA) is a multicentre prospective clinical study (UMIN000008696). In the MIMOGA study, we found that a lower percentage of CD2- CD19+ B cells in peripheral blood mononuclear cells (PBMC) was a significant unfavourable prognostic factor for overall survival (OS). Accordingly, we then analysed the immunoglobulin G (IgG) heavy-chain repertoire in PBMC by high-throughput sequencing. Of the 101 patients enrolled in the MIMOGA study, for 81 a sufficient amount of PBMC RNA was available for repertoire sequencing analysis. Peripheral IgG B cells in patients with ATL had a restricted repertoire relative to those in healthy individuals. There was a significant positive correlation between the Shannon-Weaver diversity index (SWDI) for the IgG repertoire and proportions of B cells in the PBMC of the patients. Multivariate analysis identified two variables significantly affecting OS: a higher serum soluble interleukin-2 receptor level, and a lower SWDI for the IgG repertoire [hazard ratio, 2·124; 95% confidence interval, 1·114-4·049; n = 44]. The present study documents the importance of humoral immune responses in patients receiving mogamulizumab-containing treatment. Further investigation of strategies to enhance humoral immune responses in patients with ATL is warranted.


Asunto(s)
Biomarcadores de Tumor , ADN Tumoral Circulante , Inmunoglobulina G/genética , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia-Linfoma de Células T del Adulto/genética , Leucocitos Mononucleares/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Variación Genética , Humanos , Leucemia-Linfoma de Células T del Adulto/sangre , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del Tratamiento
6.
Proc Natl Acad Sci U S A ; 116(23): 11181-11186, 2019 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-31101716

RESUMEN

Wurtzite boron nitride (w-BN) is a metastable superhard material that is a high-pressure polymorph of BN. Clarifying how the metastable high-pressure material can be stabilized at atmospheric pressure is a challenging issue of fundamental scientific importance and promising technological value. Here, we fabricate millimeter-size w-BN bulk crystals via the hexagonal-to-wurtzite phase transformation at high pressure and high temperature. By combining transmission electron microscopy and ab initio molecular dynamics simulations, we reveal a stabilization mechanism for w-BN, i.e., the metastable high-pressure phase can be stabilized by 3D networks of planar defects which are constructed by a high density of intersecting (0001) stacking faults and {10[Formula: see text]0} inversion domain boundaries. The 3D networks of planar defects segment the w-BN bulk crystal into numerous nanometer-size prismatic domains with the reverse crystallographic polarities. Our findings unambiguously demonstrate the retarding effect of crystal defects on the phase transformations of metastable materials, which is in contrast to the common knowledge that the crystal defects in materials will facilitate the occurrence of phase transformations.

7.
Rinsho Ketsueki ; 63(3): 206-210, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-35387934

RESUMEN

A 58-year-old man was diagnosed with mycosis fungoides (MF) confirmed by skin biopsy for systemic erythema that appeared in 2006 and had been on psoralen plus ultraviolet A (PUVA) therapy and topical steroids. In September 2017, he had diffuse large B-cell lymphoma and received chemotherapy. Since March 2019, tumor stage MF with large cell transformation was observed, and chemotherapy containing brentuximab vedotin (BV) was performed, which yielded a remarkable response. During the preparation for allogeneic hematopoietic stem cell transplantation, bradykinesia, delayed response, and cognitive decline were observed. Head magnetic resonance imaging fluid-attenuated inversion recovery images showed hyperintensity in the deep white matter below the bilateral frontal cortex. The general cerebrospinal fluid test revealed no abnormalities and was below the sensitivity of JC virus (JCV) quantitative PCR. As progressive multifocal leukoencephalopathy (PML) was strongly suspected from clinical symptoms and radiographic signs, ultrasensitive JCV testing was performed. The test result was positive; hence, the patient was diagnosed with PML. Chemotherapy was discontinued, but his central nervous system symptoms worsened, and he died on the 135th day of illness. We considered that PML developed based on the underlying disease and immunodeficiency caused by chemotherapy such as BV.


Asunto(s)
Virus JC , Leucoencefalopatía Multifocal Progresiva , Micosis Fungoide , Neoplasias Cutáneas , Brentuximab Vedotina , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/etiología , Imagen por Resonancia Magnética/efectos adversos , Masculino , Persona de Mediana Edad , Micosis Fungoide/complicaciones , Micosis Fungoide/terapia , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/tratamiento farmacológico
8.
Haematologica ; 105(2): 358-365, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31101757

RESUMEN

Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure.


Asunto(s)
Supervivientes a la Bomba Atómica , Síndromes Mielodisplásicos , Aberraciones Cromosómicas , Humanos , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/genética , Factores de Riesgo , Sobrevivientes
9.
Hematol Oncol ; 38(2): 162-170, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31922287

RESUMEN

Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo-HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft-versus-host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo-HSCT and need to be selected based on adverse event profiles.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Lenalidomida/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Trasplante Homólogo
10.
Rinsho Ketsueki ; 61(1): 33-38, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-32023600

RESUMEN

CD20 antigen is an important marker for diagnosis of B-cell neoplasms that is highly expressed on the surface of neoplastic B lymphocytes. Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma, of which diffuse large B-cell lymphoma (DLBCL) is the most common type. We report an unusual case of CD20-negative DLBCL complicated by rheumatoid arthritis. An 81-year old female presented with a left-sided cervical tumor, enlarged tonsil, and polyarticular pain. Pathological findings of the left tonsil showed proliferation of large atypical cells with irregular shaped nuclei. Most large cells were negative for CD3 and CD20. Additionally, these cells were positive for CD79a, BCL2, and MUM1, and negative for CD10, CD138, BCL6, PAX5, EBV-ISH, HHV8, and ALK.. Therefore, she was diagnosed with CD20-negative DLBCL complicated with RA and received dose-modified CHOP that achieved partial remission. Because CD20-negative DLBCL is rare, the identification of the clinicopathological features of this disease is urgently required.


Asunto(s)
Artritis Reumatoide , Linfoma de Células B Grandes Difuso , Anciano de 80 o más Años , Antígenos CD20 , Artritis Reumatoide/complicaciones , Biomarcadores , Femenino , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Neprilisina
11.
Blood ; 128(10): 1374-81, 2016 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-27418641

RESUMEN

Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7.4% of patients), and the other showed minimal expression in lymphoma cells (nPD-L1(-), 92.6%). Within the nPD-L1(-) group, 2 subsets emerged: the first displayed abundant PD-L1 expression in nonmalignant stromal cells of the tumor microenvironment (miPD-L1(+), 58.5%) and the second group did not express PD-L1 in any cell (PD-L1(-), 34.1%). nPD-L1(+) ATLL (median survival time [MST] 7.5 months, 95% CI [0.4-22.3]) had inferior overall survival (OS) compared with nPD-L1(-) ATLL (MST 14.5 months, 95% CI [10.1-20.0]) (P = .0085). Among nPD-L1(-) ATLL, miPD-L1(+) ATLL (MST 18.6 months, 95% CI [11.0-38.5]) showed superior OS compared with PD-L1(-) ATLL (MST 10.2 months, 95% CI [8.0-14.7]) (P = .0029). The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P = .0322 and P = .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL.


Asunto(s)
Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Leucemia-Linfoma de Células T del Adulto/patología , Células del Estroma/metabolismo , Microambiente Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Células del Estroma/patología , Tasa de Supervivencia
12.
Histopathology ; 72(6): 945-954, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29297942

RESUMEN

AIMS: Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and ß2 microglobulin (ß2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and ß2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL. METHODS AND RESULTS: We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for ß2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and ß2M in the cell membrane (HLAm+ ß2Mm+ ). No significant clinical differences other than prognosis were found between the HLAm+ ß2Mm+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1high ) (P = 0.011) of the HLAm+ ß2Mm+ group than in the other groups. The HLAm+ ß2Mm+ group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLAm+ ß2Mm+ with miPD-L1high had the most favourable prognosis among all groups. CONCLUSIONS: The membranous expression of HLA and ß2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy.


Asunto(s)
Biomarcadores de Tumor/inmunología , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/análisis , Antígeno B7-H1/biosíntesis , Biomarcadores de Tumor/análisis , Supervivencia sin Enfermedad , Femenino , Antígenos HLA/análisis , Antígenos HLA/biosíntesis , Humanos , Estimación de Kaplan-Meier , Leucemia-Linfoma de Células T del Adulto/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Microglobulina beta-2/análisis , Microglobulina beta-2/biosíntesis
14.
Haematologica ; 103(6): 1018-1028, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29242302

RESUMEN

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.


Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/fisiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Células T Asesinas Naturales/metabolismo , Células T Asesinas Naturales/virología , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Biomarcadores , Biopsia , Femenino , Humanos , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Evaluación de Síntomas , Carga Viral , Adulto Joven
15.
Eur J Haematol ; 98(5): 459-466, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28129454

RESUMEN

OBJECTIVES: T-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS. METHODS: We analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. RESULTS: T-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics. CONCLUSION: T-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.


Asunto(s)
Leucemia Prolinfocítica de Células T/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Biopsia , Niño , Diagnóstico Diferencial , Femenino , Reordenamiento Génico , Humanos , Inmunofenotipificación , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/mortalidad , Leucemia Prolinfocítica de Células T/terapia , Recuento de Leucocitos , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/mortalidad , Linfoma de Células T Periférico/terapia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Receptores de Antígenos de Linfocitos T/genética , Resultado del Tratamiento , Adulto Joven
16.
J Pathol ; 238(5): 621-6, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26847489

RESUMEN

Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.


Asunto(s)
Biomarcadores de Tumor/genética , Mutación del Sistema de Lectura , Leucemia-Linfoma de Células T del Adulto/genética , Receptores CCR4/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Receptores CCR4/análisis , Factores de Tiempo
17.
Nano Lett ; 16(9): 5409-14, 2016 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-27472440

RESUMEN

The ability to view directly the surface structures of battery materials with atomic resolution promises to dramatically improve our understanding of lithium (de)intercalation and related processes. Here we report the use of state-of-the-art scanning transmission electron microscopy techniques to probe the (010) surface of commercially important material LiFePO4 and compare the results with theoretical models. The surface structure is noticeably different depending on whether Li ions are present in the topmost surface layer or not. Li ions are also found to migrate back to surface regions from within the crystal relatively quickly after partial delithiation, demonstrating the facile nature of Li transport in the [010] direction. The results are consistent with phase transformation models involving metastable phase formation and relaxation, providing atomic-level insights into these fundamental processes.

18.
Microscopy (Oxf) ; 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38244611

RESUMEN

We demonstrated large-volume three-dimensional (3D) reconstruction using plasma focused ion beam - scanning electron microscopy (PFIB-SEM). We successfully reconstructed a 750 µm (W) × 143 µm (H) × 310 µm (D) volume at a resolution of 200 nm/pix from 1,550 SEM backscattered electron images of a Li-ion battery cathode sheet. The PFIB-SEM system was found to be capable of acquiring and reconstructing larger volume 3D datasets than X-ray computed tomography, and with higher resolution and contrast.

19.
Cells ; 13(2)2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38247820

RESUMEN

γδ T cells and natural killer (NK) cells have attracted much attention as promising effector cell subsets for adoptive transfer for use in the treatment of malignant and infectious diseases, because they exhibit potent cytotoxic activity against a variety of malignant tumors, as well as virus-infected cells, in a major histocompatibility complex (MHC)-unrestricted manner. In addition, γδ T cells and NK cells express a high level of CD16, a receptor required for antibody-dependent cellular cytotoxicity. Adult T-cell leukemia-lymphoma (ATL) is caused by human T-lymphotropic virus type I (HTLV-1) and is characterized by the proliferation of malignant peripheral CD4+ T cells. Although several treatments, such as chemotherapy, monoclonal antibodies, and allogeneic hematopoietic stem cell transplantation, are currently available, their efficacy is limited. In order to develop alternative therapeutic modalities, we considered the possibility of infusion therapy harnessing γδ T cells and NK cells expanded using a novel nitrogen-containing bisphosphonate prodrug (PTA) and interleukin (IL)-2/IL-18, and we examined the efficacy of the cell-based therapy for ATL in vitro. Peripheral blood samples were collected from 55 patients with ATL and peripheral blood mononuclear cells (PBMCs) were stimulated with PTA and IL-2/IL-18 for 11 days to expand γδ T cells and NK cells. To expand NK cells alone, CD3+ T-cell-depleted PBMCs were cultured with IL-2/IL-18 for 10 days. Subsequently, the expanded cells were examined for cytotoxicity against ATL cell lines in vitro. The proportion of γδ T cells in PBMCs was markedly low in elderly ATL patients. The median expansion rate of the γδ T cells was 1998-fold, and it was 12-fold for the NK cells, indicating that γδ T cells derived from ATL patients were efficiently expanded ex vivo, irrespective of aging and HTLV-1 infection status. Anti-CCR4 antibodies enhanced the cytotoxic activity of the γδ T cells and NK cells against HTLV-1-infected CCR4-expressing CD4+ T cells in an antibody concentration-dependent manner. Taken together, the adoptive transfer of γδ T cells and NK cells expanded with PTA/IL-2/IL-18 is a promising alternative therapy for ATL.


Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Adulto , Anciano , Humanos , Leucemia-Linfoma de Células T del Adulto/terapia , Interleucina-18 , Interleucina-2 , Leucocitos Mononucleares , Inmunoterapia , Anticuerpos Monoclonales
20.
BJS Open ; 8(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38242576

RESUMEN

BACKGROUND: The impact of computed tomography (CT)-detected extramural venous invasion on the recurrence of colon cancer is not fully understood. The aim of this study was to investigate the clinical significance of extramural venous invasion diagnosed before surgery by contrast-enhanced CT colonography using three-dimensional multiplanar reconstruction images. METHODS: Patients with colon cancer staged greater than or equal to T2 and/or stage I-III who underwent contrast-enhanced CT colonography between 2013 and 2018 at the National Cancer Center Hospital in Japan were retrospectively investigated for CT-detected extramural venous invasion. Inter-observer agreement for the detection of CT-detected extramural venous invasion was evaluated and Kaplan-Meier survival curves were plotted for recurrence-free survival using CT-TNM staging and CT-detected extramural venous invasion. Preoperative clinical variables were analysed using Cox regression for recurrence-free survival. RESULTS: Out of 922 eligible patients, 544 cases were analysed (50 (9.2 per cent) were diagnosed as positive for CT-detected extramural venous invasion and 494 (90.8 per cent) were diagnosed as negative for CT-detected extramural venous invasion). The inter-observer agreement for CT-detected extramural venous invasion had a κ coefficient of 0.830. The group positive for CT-detected extramural venous invasion had a median follow-up of 62.1 months, whereas the group negative for CT-detected extramural venous invasion had a median follow-up of 60.7 months. When CT-TNM stage was stratified according to CT-detected extramural venous invasion status, CT-T3 N(-)extramural venous invasion(+) had a poor prognosis compared with CT-T3 N(-)extramural venous invasion(-) and CT-stage I (5-year recurrence-free survival of 50.6 versus 89.3 and 90.1 per cent respectively; P < 0.001). In CT-stage III, the group positive for CT-detected extramural venous invasion also had a poor prognosis compared with the group negative for CT-detected extramural venous invasion (5-year recurrence-free survival of 52.0 versus 78.5 per cent respectively; P = 0.003). Multivariable analysis revealed that recurrence was associated with CT-T4 (HR 3.10, 95 per cent c.i. 1.85 to 5.20; P < 0.001) and CT-detected extramural venous invasion (HR 3.08, 95 per cent c.i. 1.90 to 5.00; P < 0.001). CONCLUSION: CT-detected extramural venous invasion was found to be an independent predictor of recurrence and could be used in combination with preoperative TNM staging to identify patients at high risk of recurrence.


Asunto(s)
Neoplasias del Colon , Colonografía Tomográfica Computarizada , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias del Colon/patología , Estadificación de Neoplasias
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